Pregnancy after bariatric surgery: a narrative literature review and discussion of impact on pregnancy management and outcome

Bariatric surgery might be indicated if other attempts of losing weight have failed. It is the most effective way for weight loss and the reduction of comorbidities like type II diabetes mellitus [11] and hypertension [12] and has favourable effects on cardiac function [13, 14]. International guidelines stipulate that BS should be considered if a patient’s BMI exceeds 40 kg/m², or in case of a BMI between 35 kg/m² and 40 kg/m² with associated severe comorbidities; in the case of coexisting diabetes mellitus even in the case of a BMI between 30 kg/m² and 35 kg/m² [3].

BS is divided into restrictive and malabsorptive procedures or a combination of both. The most widely used surgical procedures are the Roux-en-Y gastric bypass (RYGB), the sleeve gastrectomy and the adjustable gastric band. Other techniques such as the biliopancreatic diversion are not very common and will therefore not be discussed in this review. RYGB (Fig. 1a) is a combined malabsorptive and restrictive procedure which consists of a horizontal partitioning of the upper part of the stomach to create a gastric pouch. 75 to 150 cm of the small intestine are used to create the alimentary limb which carries ingested food to the bowel without the addiction of biliopancreatic secretions which are carried directly into the bowel through the biliopancreatic limb, typically 30 to 60 cm in length [15].

Sleeve gastrectomy (Fig. 1b) is a restrictive procedure and is performed as laparoscopic gastric resection which creates a small gastric pouch. It can be combined with the duodeno-ileostomy as part of a biliopancreatic bypass [15].

Adjustable gastric banding (Fig. 1c) is normally performed as a laparoscopic procedure (LAGB) and consists in placing a band 1 to 2 cm below the gastroesophageal junction, creating an upper gastric pouch with a capacity of 20 to 30 mL. The degree of constriction of the stomach can be adjusted by the introduction of saline through the port [15].

Other less frequent procedures, such as the biliopancreatic diversion, will not be discussed in this paper.

By the endoscopic placement of intragastric balloons with a volume of at least 400 ml gastric space is occupied and gastric motility is altered [16]. Compared to standard bariatric surgery, bariatric endoscopy (BE) is considered to be less invasive, more economic and associated with lower morbidity and mortality. Depending on individual circumstances, it might also be approved for patients with a BMI between 30 and 35 kg/m² [16, 17]. Furthermore, the procedure can be repeated if necessary [17]. Bariatric endoscopy is associated with beneficial metabolic effects like reduced incidence of hyperuricemia, hypertriglyceridemia, hypercholesterolemia and diabetes mellitus [18]. To our knowledge there is currently only one retrospective study that investigated if BE has potential benefits for patients with obesity-induced infertility. The authors showed that 15 out of 27 obese women conceived successfully after the placement of an intragastric balloon and subsequent weight loss. All pregnancies were uneventful and ended with life births; however, further research is needed before concluding that BE is safe in reproductive age and pregnancy [19].

The references for this review were obtained from Pubmed and MedLine databases using the MeSH Terms: “obesity”, “bariatric surgery”, “pregnancy and bariatric surgery”, “obesity and fertility”, “obesity and pharmacology”, “obesity and bariatric surgery”, “obesity and diabetes”, “diabetes and pregnancy”, “gestational diabetes and hypertension”, “obesity and hypertension”, “bariatric surgery and hypertension”, “obesity and heart disease”, “bariatric surgery and heart disease”, “gastric bypass and anaemia”, “gastric bypass and hyperparathyroidism”, “bariatric surgery and vitamin D”, “dietary supplements and gastric bypass”, “gastric bypass and abdominal hernia”, “fetal macrosomia”, “infant, small for gestational age, breastfeeding and bariatric surgery”. We prioritized longitudinal observational studies, cohort studies and meta-analysis. Furthermore, we used clinical guidelines from the American Congress of Obstetricians and Gynaecologists (ACOG) for the management of pregnancy and delivery after bariatric surgery and the Scientific Impact Paper on the role of bariatric surgery in improving reproductive health by the Royal College of Obstetricians and Gynaecologists.

Obesity was shown to impact fertility on various levels by affecting endometrial and ovarian function [33‐35]. Insulin resistance and compensatory hyperinsulinemia adversely affect intraovarian follicle growth and oocyte maturation, leading to oligo-/amenorrhea, hyperandrogenemia and polycystic ovarian syndrome (PCOS) [36, 37]. Consequently, a close interaction of impaired reproductive and metabolic features can be observed in obese women [38]. Hence, even at a young age, assisted reproductive technology (ART) is often required in obese patients to achieve a live-birth. The accompanying technical procedures such as ovarian ultrasound visualization or oocyte retrieval might be complicated by excess body weight [35]. Even when ART can be performed, obesity was associated with impaired treatment outcome including less collected oocytes after ovarian hyperstimulation, lower embryo quality, reduced pregnancy and live-birth rates and high miscarriage rates. Although the available data is still inconclusive, it seems that those impaired ART outcomes are attributable to obesity and not to underlying pathologies such as PCOS [39]. Therefore, in accordance with the general BS guidelines [3] and depending on the individual patient’s metabolic and reproductive profile, BS might be considered in infertile anovulatory patients with a BMI > 35 kg/m² and no effect of life-style intervention for at least 6 months [40]. Bariatric surgery was shown to ameliorate hyperandrogenemia and PCOS in a majority of patients [41]. In patients trying to conceive after BS, one meta-analysis reported up to 58% spontaneous conception rates [42]. Moreover, self-esteem and sexual functioning are increasing following BS induced weight-loss [43]. Even patients undergoing ART before and after BS showed increased numbers of retrieved oocytes, improved oocyte quality and live-birth rates [44]. However, risks and benefits of BS at childbearing age should be carefully balanced, in order to improve maternal health and to reduce the risk of long-lasting health consequences in the offspring [35]. BS should not be regarded as a primary infertility treatment [23].

Gestational Diabetes Mellitus (GDM) is defined as “diabetes first diagnosed in the second or third trimester of pregnancy that is not clearly either preexisting type 1 or type 2 diabetes” [88] and affects approximately 6% of pregnancies in Europe [89]. Most recent guidelines recommend universal testing for GDM between 24 + 0 and 28 + 6 weeks of gestation by a 2 h 75 g oral glucose tolerance test (OGTT) [88]. The International Association of Diabetes in Pregnancy Study Group (IADPSG) established the following diagnostic thresholds: fasting plasma glucose ≥5.1 mmol/l (92 mg/dl), or 1-h plasma glucose ≥10.0 mmol/l (180 mg/dl), or 2-h plasma glucose ≥8.5 mmol/l (153 mg/dl) [90]. However, the diagnosis of GDM still remains controversial, as other diagnostic algorithms and thresholds are still in use [91], leading to heterogeneity in study results and epidemiologic data [89].

Obesity is a risk factor for the development of GDM. Compared to normal weight women, the OR for GDM was found to be 1.97 in overweight women (pre-pregnancy BMI 25 to 30), 3.01 in moderately obese (BMI 30 to 35) and 5.55 in severely obese women (BMI > 35) [92]. The mechanisms which link obesity and GDM are still a target of research, but the enhanced secretion of pro-inflammatory cytokines by adipose tissue and subsequent systemic inflammatory and immune dysregulation seems to increase the maternal insulin resistance [93, 94].

GDM is associated with a number of adverse pregnancy outcomes, especially cesarean section, large for gestational age, macrosomia and preeclampsia [91, 95]. Moreover, children of diabetic mothers seem to have an increased risk of developing obesity and metabolic dysfunction later in life [8, 96, 97] due to “metabolic imprinting”, e.g. the in-utero alteration of fetal organ function as a consequence of an excessive supply of nutrients and subsequently enhanced exposure to growth factors [96, 97].

BS before pregnancy seems to reduce the risk for developing GDM considerately [22, 52, 98‐102]. Galazis et al. found the overall incidence of GDM as being approximately half in women after BS compared to controls [52]. However, results vary depending on control group and diagnostic criteria (see Table 1).

Despite the protective effect of BS and subsequent weight loss on the development of GDM, some procedures like RYGB alter glucose kinetics and might also have detrimental effects on pregnancy outcome and GDM diagnostics which have to be observed by obstetricians.

As previously observed in non-pregnant patients, some bariatric procedures (like RYGB and sleeve gastrectomy) are characterized by an exaggerated postprandial rise of plasma glucose concentrations followed by hyperinsulinemic hypoglycemia [103]. To provide first insights into the possible effects of gastric bypass surgery on glucose metabolism during pregnancy, we retrospectively assessed maternal characteristics of 76 pregnant women after gastric bypass. The data included results of a 2 h 75 g OGTT with measurements at fasting as well after 60 and 120 min after oral glucose load. We found that women after gastric bypass had improved fasting glucose, but altered patterns of postprandial glucose dynamics including a rise at 60 min, followed by hypoglycemia at 120 min in more than half of pregnant patients [28]. Our results were recently confirmed by another prospective cohort study on 25 pregnant women after RYGB, indicating that the recommended diagnosis criteria for GDM are not reliable after BS [104]. Obstetricians should consider other diagnostic approaches such as frequent capillary blood glucose measurements or continuous subcutaneous glucose monitoring (CGMS) in these patients; however, there are no guidelines yet [23, 24, 35, 105]. Only one study reported CGMS profiles of 35 pregnant women after RYGB and reported abnormal glucose variability in real-life conditions as well [106]. Therefore, obstetricians should be aware of symptoms indicative of dumping syndrome. The early dumping syndrome occurs within 15 min to 1 h after a meal rich in simple carbohydrates. The rapid emptying of hyperosmolar carbohydrates into the small intestine leads to a fluid shift from plasma to bowel, causing a drop in blood pressure and subsequent compensation, leading to vasomotor symptoms such as flushing, palpitation, perspiration, tachycardia, hypotension and syncope [107, 108]. Patients should be advised to consume smaller meals rich in complex carbohydrates, to delay liquid intake until at least 30 min after a meal and to lie down after eating to delay the gastric emptying into the small intestine [108]. The late dumping syndrome, with an onset of symptoms 2 to 3 h after a meal, is supposed to be caused by an excessive insulin response following the rapid glucose transit into the jejunum and subsequent reactive hypoglycemia [107, 108]. The symptoms include sweating, tremulousness, poor concentration, altered consciousness, palpitations and syncope. The main therapeutic intervention is a dietary modification eliminating refined carbohydrates. Pectin or guar gum can be added to increase viscosity of food but are poorly accepted due to their unpalatability. Diaxozide decreases the insulin release and has been reported to ameliorate the condition but is not safe in pregnancy; somatostatin analogues and acarbose are not well tested in pregnant human individuals and there is only one case report on successful treatment of late dumping syndrome with acarbose in a pregnant woman [107]. Obstetricians should seek advice from bariatric specialists if their pregnant patients present with symptoms indicative of dumping syndrome.

Hypertensive disorders in pregnancy include pre-gestational chronic hypertension, pregnancy-induced hypertension (PIH) and preeclampsia (PE). PE is defined as de novo onset of hypertension (> 140 mmHg systolic or > 90 mmHg diastolic) after 20 weeks gestation and the coexistence of at least one of the following conditions: proteinuria, other maternal organ dysfunction such as renal insufficiency, liver involvement or neurological complications or utero-placental dysfunction (fetal growth retardation) [109]. Hypertensive disorders affect approximately 10% [110] of all pregnancies and account for 14% of maternal deaths worldwide [111]. Its incidence is on the rise, with a 21% increase in inpatient deliveries involving PE between 2005 and 2014 in the USA [112]. Several authors attribute the increasing PE incidence to the obesity pandemic [113‐115]. Mbah et al. report a positive association between PE incidence and pre-pregnancy BMI as well as pregnancy weight gain rate, with 3.3% of normal weight mothers being affected, 7.7% of mothers with class I obesity, 9.5% of mothers with class II obesity, 10.9% of mothers with class III obesity and 13.4% of super obese gravidas (BMI ≥ 50 kg/m²). In comparison to normal weight mothers, obese women had a three-fold increased risk for the development of PE [113]. Although the mechanisms by which obesity increases the risk for hypertensive disorders are not fully understood yet, it seems that obesity-related metabolic factors cause cytotrophoblast dysfunction and subsequent placental ischemia, thereby increasing the release of soluble placental factors and enhancing the sensitivity by which those factors cause endothelial dysfunction and hypertension [115]. With BS being the most effective treatment for obesity, it can be assumed that women who conceive after BS have a lower risk for developing hypertension disorders and the available data support this presumption. One study compared women who delivered before an already planned BS with women who delivered after BS. Almost 15% of women who delivered before BS had PE compared to only 3% of those who delivered after BS. Rates of PIH were also lower in the post-surgery group (2.5% versus 13.0%), resulting in a 75% lower odds to be diagnosed with a hypertensive disorder for women after surgery [116]. Several reviews and meta-analysis [22, 98‐102, 117] come to the same conclusion. Yi et al. [102] report an overall OR of 0.42 for the diagnosis of hypertensive disorders in pregnancies after BS, with a significantly less OR (0.14) when conception took place within the first 2 years after surgery. Vrebosch et al. [99] come to the conclusion that the incidence of PE and PIH are lower in post-surgical women compared to obese non-surgical controls, but still higher than in normal weight women without BS, but only reviewed laparoscopic adjustable gastric banding studies. Ducarme et al. [118] found evidence that PE rates were lower in women after BS, but not different for PIH. Although the available data indicates that gravidas after BS are at significantly lower risk for the diagnosis of hypertension disorders, further research is needed, especially concerning the impact of different surgical procedures and surgery-conception time.

Pregnancy may expose women after BS to a higher risk of developing internal herniation due to the fact that the enlarged uterus lifts up the bowel, resulting in increased intra-abdominal pressure [24, 30]. In the case of acute abdominal pain, immediate surgical intervention must be considered, also when pregnancy has to be carried on [24, 30, 31, 119]. Of note, internal hernia after RYGB is not rare, with an incidence of up to 10% [30]. The most common internal hernias develop in the the transverse mesocolon defect, the Petersen’s space and the mesenteric defect underneath jejunu-jejunalis anastomosis [120]. Petersen’s hernia is a retroanastomotic hernia where the small bowel moves into the space between the caudal surface of the transverse mesocolon and the edge of the Roux limb and can rapidly lead to acute bowel obstruction with necrosis. In this case an immediate emergency surgery has to be performed [121]. Patients who are suspected to have developed an internal hernia are requested to fast during observation. If the abdominal pain relapses after the ingestion of food a subacute operation has to be considered. If the pain is constantly present in spite of fasting, an emergency operation (detorsion or bowel resection) is necessary and should be performed as fast as possible to minimize the risk of bowel necrosis and severe maternal and fetal complications [122].

Obesity during pregnancy might be associated with a higher risk of fetal malformations like neurological defects, congenital heart defects and orofacial clefts. Furthermore, some data indicate that the risk of miscarriage and intrauterine fetal death could be increased [4]. A systematic review and meta-analysis assessed the risk of congenital anomalies in the offspring of obese pregnant women compared to lean pregnant women and found that neonates of obese women have a higher risk of neural tube defects (anencephaly OR: 1.39, CI: 1.03–1.87, spina bifida OR: 2.24, CI: 1.86–2.69), cardiovascular defects (OR: 1.30, CI: 1.12–1.51), and other congenital abnormalities such as anorectal atresia (OR 1.48, CI: 1.12–1.97), compared to pregnant women with normal BMI [7]. More recent studies come to similar conclusions [123].To date, the role of obesity in inducing fetal malformations is not fully understood and may reflect the difficulty of prenatal diagnosis at early pregnancy, due to obesity-related procedural difficulties. Further research is needed to elucidate the relationship between obesity and fetal malformations [123, 124].

It is widely known that maternal obesity could lead to LGA offspring, which poses a high risk for complications during labour, like shoulder dystocia [125], and also to long-term health consequences, like obesity in childhood, diabetes and cardiovascular diseases [126]. Thus, it is reasonable to investigate if BS and consequent weight lost could also influence the children of mothers with a history of BS.

A Swedish national cohort study investigated the outcomes of 670 singleton pregnancies of post-surgical women and detected that pregnant women who underwent BS have a lower risk of gestational diabetes and large for gestational age (LGA) neonates, but a higher risk of SGA infants. No significant difference in the frequency of fetal malformations was found [29].

Several other studies (Table 2) found an increased risk of SGA infants born to mothers after malabsorptive or mixed bariatric surgeries [22, 52, 100, 102, 117], but not after solely restrictive procedures [52, 99]. The pathophysiology of this phenomenon requires further elucidation, but there seems to be an association between low maternal glucose levels in glucose challenge or oral glucose tolerance tests and SGA fetuses [95, 127]. An association between lower neonatal weight, glucose nadir and increased insulin release during an OGTT was most recently observed by our study group in offspring of mothers after RYGB [104]. In addition, Gascoin et al. found a significant inverse correlation between birth weight and length and maternal weight loss between surgery and pregnancy (the greater the weight loss the lower the birth weight and length). There were also low cord blood IGF1 and Leptin levels in infants from RYGB mothers, hinting to a decreased anabolism in those infants [63]. Low birth weight seems to have detrimental effects on the offspring even in adulthood. Being born SGA is considered to be a risk factor for the development of insulin resistance and type 2 diabetes, the metabolic syndrome and cardiovascular diseases [128], possibly due to fetal programming by changes in the intrauterine environment in malnourished mothers (thrifty phenotype hypothesis) [129]. Therefore, it might even be considered to prefer restrictive over malabsorptive BS techniques in young women who have a desire to bear children to avoid those complications [52].

However, two retrospective studies conducted in Israel and in France compared fetal birth weight after malabsorptive and restrictive procedures and found no statistically significant difference in SGA rates between the two groups [130, 131].

Human breast milk is a rich source of carbohydrates, protein, fat, vitamins, minerals, digestive enzymes and hormones (87% water, 3.8% fat, 1.0% protein, and 7% lactose). Additionally, it contains a vast amount of other, at least partially bioactive compounds, such as immune cells and human milk oligosaccharides (HMOs). These HMOs were found to exert antibacterial effects in the infant’s gastrointestinal tract. Regarding micro-nutrition, human milk supplies sufficient amounts of all vitamins except Vitamin D and vitamin K. Therefore, the lack of these two vitamins carries out some risk of deficiency for the infant [132].

Vitamin B12 deficiency might be a problem in breastfed infants born to women after gastric bypass, potentially leading to detrimental consequences such as polycythemia or megaloblastic anemia [133]. As observed in one case the milk secreted by lactating women after gastric bypass could be of lower nutritional density, especially in milk fats. This could lead to delayed growth of the children when breastfed exclusively as it was observed in one case report [134]. However, breastfeeding is known to prevent several infectious, atopic and cardiovascular diseases. Breastfeeding may also reduce the risk of respiratory infections, asthma, leukaemia and sudden infant death syndrome [135]. It also provides positive effects on brain and neuronal development and might be associated with a higher IQ [136]. Other studies concluded that exclusive breastfeeding for longer than six months may reduce the risk of obesity in later life [137]. As there is very little evidence regarding nutrient deficiencies in breast milk after BS, it is reasonable to recommend bariatric patients to breastfeed their infants [24, 138]. The above-mentioned positive effects of human breast milk most likely outweigh any BS related deficiency. However, there is no international consensus regarding vitamin or micronutrient supplementation during the lactational period after BS and healthcare professionals should take the patients history of BS into consideration when their infants present with symptoms of any nutritional deficiency.

The limitations of this study result from its narrative approach. Compared to systematic reviews or meta-analysis, narrative reviews are characterized by subjective study selection and weighing. Inclusion criteria and study characteristics are mostly unspecified which may cause misleading in drawing conclusions. To be able to elaborate objective guidelines for the management of pregnancies after BS, systematic reviews and meta-analysis should be performed.